SUBSTANCE P IN CARDIOVASCULAR REGULATION

P 物质在心血管调节中的作用

• 批准号: 3345496
• 负责人: JOHN M STEWART
• 金额: $ 14.31万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-04-01 至 1993-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3345496
• 关键词: autonomic reflex; baroreceptors; blood pressure; calcitonin gene related peptide; central nervous system; endopeptidases; glutamates; high performance liquid chromatography; hypertension; inhibitor /antagonist; laboratory rat; microinjections; neural transmission; neuropeptide Y; neuropharmacology; peptide chemical synthesis; protein structure function; stimulant /agonist; substance P; tachykinin

This project studies the role of the neuropeptide substance P (SP) in CNS regulation of blood pressure and possible abnormalities of this system in hypertension. Much evidence supports a role for SP as a neurotransmitter or neuromodulator of the baroreflex arc, the principal mechanism for instantaneous physiological regulation of blood pressure. SP apparently functions in this system at both afferent and efferent levels. SP appears to exert its neurotransmitter and/or neuromodulator effects in the CNS only after processing by enzymes which yield active N-terminal or C-terminal fragments. The N-terminal fragment SP(1-7) is produced by the endopeptidase 3.4.24.11 and appears to be a neurotransmitter for afferents from the carotid sinus and aortic arch which terminate in the nucleus tractus solitarius (NTS), while the C-terminal fragment SP(5-11) is produced by the post-proline cleaving enzyme and elevates blood pressure by stimulation of sympathetic outflow. SP(1-7) fulfills many of the criteria for being a neurotransmitter in the baroreflex arc. This project studies the role(s) of SP(1-7) in this system. Peptides related to SP(1-7) are synthesized in the search for antagonists and potent, long-acting agonists. These peptides are injected into the NTS to study their effect on blood pressure and functioning of the baroreflex. Antisera against the peptides and the processing enzymes will also be used. Other tachykinins and the neuropeptides calcitonin gene related peptide (CGRP) and neuropeptide Y (NPY) will also be studied. Interaction of SP and SP(1-7) with glutamate, which also fulfills many criteria for a neurotransmitter in this system, will be studied with specific glutamate agonists and antagonists. Other candidate neurotransmitter amino acids will also be studied.

本课题研究神经肽P物质（SP）在中枢神经系统中的作用 调节血压和这个系统可能的异常， 高血压许多证据支持SP作为神经递质或 压力反射弧的神经调质， 血压的瞬时生理调节。SP显然 在传入和传出两个层次上在这个系统中起作用。SP出现 仅在CNS中发挥其神经递质和/或神经调质作用 在通过产生活性N-末端或C-末端的酶处理后， 片段N-末端片段SP（1 - 7）由内肽酶产生 3.4.24.11 颈动脉窦和主动脉弓终止于束核 而C-末端片段SP（5 - 11）是由孤束孢菌（NTS）产生的。 后脯氨酸裂解酶和升高血压的刺激 交感神经流出SP（1 - 7）满足了成为一个 压力反射弧中的神经递质。 该项目研究SP（1 - 7）在该系统中的角色。肽 在寻找拮抗剂时合成了与SP（1 - 7）相关的5-氨基-1，4-二氢 强效长效激动剂将这些肽注射到NTS中， 研究它们对血压和压力反射功能的影响。 还将使用针对肽和加工酶的抗血清。 其他速激肽类和神经肽类降钙素基因相关肽 （CGRP）和神经肽Y（NPY）也将被研究。SP与 SP（1 - 7）与谷氨酸，这也符合许多标准， 在这个系统中的神经递质，将与特定的谷氨酸盐研究 激动剂和拮抗剂。其他候选神经递质氨基酸将 也被研究。